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  • 1. Abel, K. M.
    et al.
    Heuvelman, H. P.
    Joergensen, L.
    Magnusson, C.
    Wicks, S.
    Susser, E.
    Hallqvist, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Dalman, C.
    Severe bereavement stress during the prenatal and childhood periods and risk of psychosis in later life: population based cohort study2014In: The BMJ, E-ISSN 1756-1833, Vol. 348, p. f7679-Article in journal (Refereed)
    Abstract [en]

    Objective To examine the risk of psychosis associated with severe bereavement stress during the antenatal and postnatal period, between conception to adolescence, and with different causes of death. Design Population based cohort study. Setting Swedish national registers including births between 1973 and 1985 and followed-up to 2006. Participants In a cohort of 1 045 336 Swedish births (1973-85), offspring born to mothers exposed to severe maternal bereavement stress six months before conception or during pregnancy, or exposed to loss of a close family member subsequently from birth to 13 years of age were followed until 2006. Admissions were identified by linkage to national patient registers. Main outcome measures Crude and adjusted odds ratios for all psychosis, non-affective psychosis, and affective psychosis. Results Maternal bereavement stress occurring preconception or during the prenatal period was not associated with a significant excess risk of psychosis in offspring (adjusted odds ratio, preconception 1.24, 95% confidence interval 0.96 to 1.62; first trimester 0.95, 0.58 to1.56; second trimester 0.79, 0.46 to 1.33; third trimester 1.14, 0.78 to 1.66). Risks increased modestly after exposure to the loss of a close family member from birth to adolescence for all psychoses (adjusted odds ratio 1.17, 1.04 to 1.32). The pattern of risk was generally similar for non-affective and affective psychosis. Thus estimates were higher after death in the nuclear compared with extended family but remained non-significant for prenatal exposure; the earlier the exposure to death in the nuclear family occurred in childhood (all psychoses: adjusted odds ratio, birth to 2.9 years 1.84, 1.41 to 2.41; 3-6.9 years 1.47, 1.16 to 1.85; 7-12.9 years 1.32, 1.10 to 1.58) and after suicide. Following suicide, risks were especially higher for affective psychosis (birth to 2.9 years 3.33, 2.00 to 5.56; 6.9 years 1.84, 1.04 to 3.25; 7-12.9 years 2.68, 1.84 to 3.92). Adjustment for key confounders attenuated but did not explain associations with risk. Conclusions Postnatal but not prenatal bereavement stress in mothers is associated with an increased risk of psychosis in offspring. Risks are especially high for affective psychosis after suicide in the nuclear family, an effect that is not explained by family psychiatric history. Future studies are needed to understand possible sources of risk and resilience so that structures can be put in place to support vulnerable children and their families.

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  • 2.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Andersson, Dan
    Domellöf, Magnus
    Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial2011In: The BMJ, E-ISSN 1756-1833, Vol. 343, p. d7157-Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on infant iron status at 4 months of age in a European setting.

    Design: Randomised controlled trial.

    Setting: Swedish county hospital.

    Participants: 400 full term infants born after a low risk pregnancy.

    Intervention: Infants were randomised to delayed umbilical cord clamping (>= 180 seconds after delivery) or early clamping (<= 10 seconds after delivery).

    Main outcome measures: Haemoglobin and iron status at 4 months of age with the power estimate based on serum ferritin levels. Secondary outcomes included neonatal anaemia, early respiratory symptoms, polycythaemia, and need for phototherapy.

    Results: At 4 months of age, infants showed no significant differences in haemoglobin concentration between the groups, but infants subjected to delayed cord clamping had 45% (95% confidence interval 23% to 71%) higher mean ferritin concentration (117 mu g/L v 81 mu g/L, P<0.001) and a lower prevalence of iron deficiency (1 (0.6%) v 10 (5.7%), P=0.01, relative risk reduction 0.90; number needed to treat=20 (17 to 67)). As for secondary outcomes, the delayed cord clamping group had lower prevalence of neonatal anaemia at 2 days of age (2 (1.2%) v 10 (6.3%), P=0.02, relative risk reduction 0.80, number needed to treat 20 (15 to 111)). There were no significant differences between groups in postnatal respiratory symptoms, polycythaemia, or hyperbilirubinaemia requiring phototherapy.

    Conclusions: Delayed cord clamping, compared with early clamping, resulted in improved iron status and reduced prevalence of iron deficiency at 4 months of age, and reduced prevalence of neonatal anaemia, without demonstrable adverse effects. As iron deficiency in infants even without anaemia has been associated with impaired development, delayed cord clamping seems to benefit full term infants even in regions with a relatively low prevalence of iron deficiency anaemia.

  • 3.
    Andrae, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Andersson, Therese M-L
    Lambert, Paul C
    Kemetli, Levent
    Silfverdal, Lena
    Strander, Björn
    Ryd, Walter
    Dillner, Joakim
    Törnberg, Sven
    Sparén, Pär
    Screening and cervical cancer cure: population based cohort study2012In: The BMJ, E-ISSN 1756-1833, Vol. 344, p. e900-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine whether detection of invasive cervical cancer by screening results in better prognosis or merely increases the lead time until death.

    DESIGN: Nationwide population based cohort study.

    SETTING: Sweden.

    PARTICIPANTS: All 1230 women with cervical cancer diagnosed during 1999-2001 in Sweden prospectively followed up for an average of 8.5 years.

    MAIN OUTCOME MEASURES: Cure proportions and five year relative survival ratios, stratified by screening history, mode of detection, age, histopathological type, and FIGO (International Federation of Gynecology and Obstetrics) stage.

    RESULTS: In the screening ages, the cure proportion for women with screen detected invasive cancer was 92% (95% confidence interval 75% to 98%) and for symptomatic women was 66% (62% to 70%), a statistically significant difference in cure of 26% (16% to 36%). Among symptomatic women, the cure proportion was significantly higher for those who had been screened according to recommendations (interval cancers) than among those overdue for screening: difference in cure 14% (95% confidence interval 6% to 23%). Cure proportions were similar for all histopathological types except small cell carcinomas and were closely related to FIGO stage. A significantly higher cure proportion for screen detected cancers remained after adjustment for stage at diagnosis (difference 15%, 7% to 22%).

    CONCLUSIONS: Screening is associated with improved cure of cervical cancer. Confounding cannot be ruled out, but the effect was not attributable to lead time bias and was larger than what is reflected by down-staging. Evaluations of screening programmes should consider the assessment of cure proportions.

  • 4.
    Awor, Phyllis
    et al.
    Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
    Peterson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Makerere Univ, Sch Publ Hlth, Kampala, Uganda;Unicef, New York, NY USA.
    Gautham, Meenakshi
    London Sch Hyg & Trop Med, London, England.
    Delivering child health interventions through the private sector in low and middle income countries: challenges, opportunities, and potential next steps2018In: The BMJ, E-ISSN 1756-1833, Vol. 362, article id k2950Article, review/survey (Refereed)
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  • 5.
    Bjorck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Surgery for ruptured abdominal aortic aneurysm: trial reports comparable short term survival after open or endovascular repair2014In: The BMJ, E-ISSN 1756-1833, Vol. 348, p. g95-Article in journal (Other academic)
  • 6.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Endovascular or open repair for ruptured abdominal aortic aneurysm?2017In: The BMJ, E-ISSN 1756-1833, Vol. 359, article id j5170Article in journal (Other academic)
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  • 7.
    Blease, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Healthcare Sciences and e-Health. Digital Psychiatry, Division of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, USA.
    When patients are victims: access to online records and medical misconduct2022In: The BMJ, E-ISSN 1756-1833, Vol. 379, article id o2968Article in journal (Other academic)
  • 8.
    Blease, Charlotte
    et al.
    Division of General Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
    McMillan, Brian
    Salmi, Liz
    Davidge, Gail
    Delbanco, Tom
    Primary care adapting to transparent medical records: Suggestions reflecting international experience with open notes2022In: The BMJ, E-ISSN 1756-1833, article id e069861Article in journal (Refereed)
  • 9.
    Boden, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lundgren, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Brandt, Lena
    Reutfors, Johan
    Andersen, Morten
    Kieler, Helle
    Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study2012In: The BMJ, E-ISSN 1756-1833, Vol. 345, p. e7085-Article in journal (Refereed)
    Abstract [en]

    Objective To investigate the risks of adverse pregnancy and birth outcomes for treated and untreated bipolar disorder during pregnancy. Design Population based cohort study using data from national health registers. Setting Sweden. Participants 332 137 women with a last menstrual period anytime after 1 July 2005 and giving birth anytime before the end of 31 December 2009. Women with a record of at least two bipolar diagnoses were identified and grouped as treated (n=320)-those who had filled a prescription for mood stabilisers (lithium, antipsychotics, or anticonvulsants) during pregnancy-or untreated (n=554). Both groups were compared with all other women giving birth (n=331 263). Main outcome measures Preterm birth, mode of labour initiation, gestational diabetes, infants born small or large for gestational age, neonatal morbidity, and congenital malformations. Results Of the untreated women, 30.9% (n=171) were induced or had a planned caesarean delivery compared with 20.7% (n=68 533) without bipolar disorder (odds ratio 1.57, 95% confidence interval 1.30 to 1.90). The corresponding values for the treated women were 37.5% (n=120) (2.12, 1.68 to 2.67). The risks of preterm birth in both treated and untreated women were increased by 50%. Of the untreated women, 3.9% (n=542) had a microcephalic infant compared with 2.3% (324 844) of the women without bipolar disorder (1.68, 1.07 to 2.62). The corresponding values for the treated women were 3.3% (n=311) (1.26, 0.67 to 2.37). Similar trends were observed for risks of infants being small for gestational age infants for weight and length. Among infants of untreated women, 4.3% (n=24) had neonatal hypoglycaemia compared with 2.5% (n=8302) among infants of women without bipolar disorder (1.51, 1.04 to 2.43), and 3.4% (n=11) of the treated women (1.18, 0.64 to 2.16). The analyses of variation in outcomes did not support any significant differences between treated and untreated women. Conclusions Bipolar disorder in women during pregnancy, whether treated or not, was associated with increased risks of adverse pregnancy outcomes.

  • 10.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Ahlbom, Anders
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wolk, Alicja
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort2009In: The BMJ, E-ISSN 1756-1833, Vol. 338, p. b688-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine how change in level of physical activity after middle age influences mortality and to compare it with the effect of smoking cessation. DESIGN: Population based cohort study with follow-up over 35 years. SETTING: Municipality of Uppsala, Sweden. PARTICIPANTS: 2205 men aged 50 in 1970-3 who were re-examined at ages 60, 70, 77, and 82 years. MAIN OUTCOME MEASURE: Total (all cause) mortality. RESULTS: The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. Men who increased their physical activity level between the ages of 50 and 60 continued to have a higher mortality rate during the first five years of follow-up (adjusted hazard ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high physical activity). After 10 years of follow-up their increased physical activity was associated with reduced mortality to the level of men with unchanged high physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low physical activity) was similar to that associated with smoking cessation (0.64, 0.53 to 0.78, compared with continued smoking). CONCLUSIONS: Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation.

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  • 11.
    Cars, Otto
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Högberg, Liselotte Diaz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Murray, Mary
    Nordberg, Olle
    Sivaraman, Satya
    Lundborg, Cecilia Stålsby
    So, Anthony D.
    Tomson, Göran
    Meeting the challenge of antibiotic resistance2008In: The BMJ, E-ISSN 1756-1833, Vol. 337, no a1438Article in journal (Other academic)
  • 12.
    Cerani, Agustin
    et al.
    McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, 3755 Cote Ste Catherine Rd,Suite H-413, Montreal, PQ H3T 1E2, Canada.
    Zhou, Sirui
    McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, 3755 Cote Ste Catherine Rd,Suite H-413, Montreal, PQ H3T 1E2, Canada.
    Forgetta, Vincenzo
    McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
    Morris, John A.
    McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
    Trajanoska, Katerina
    Univ Med Ctr, Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Univ Med Ctr, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Rivadeneira, Fernando
    Univ Med Ctr, Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Univ Med Ctr, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Larsson, Susanna C.
    Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, Stockholm, Sweden.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Richards, J. Brent
    McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, 3755 Cote Ste Catherine Rd,Suite H-413, Montreal, PQ H3T 1E2, Canada;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
    Genetic predisposition to increased serum calcium, bone mineral density, and fracture risk in individuals with normal calcium levels: mendelian randomisation study2019In: The BMJ, E-ISSN 1756-1833, Vol. 366, article id l4410Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine if genetically increased serum calcium levels are associated with improved bone mineral density and a reduction in osteoporotic fractures. DESIGN Mendelian randomisation study.

    SETTING: Cohorts used included: the UK Biobank cohort, providing genotypic and estimated bone mineral density data; 25 cohorts from UK, USA, Europe, and China, providing genotypic and fracture data; and 17 cohorts from Europe, providing genotypic and serum calcium data (summary level statistics).

    PARTICIPANTS: A genome-wide association meta-analysis of serum calcium levels in up to 61 079 individuals was used to identify genetic determinants of serum calcium levels. The UK Biobank study was used to assess the association of genetic predisposition to increased serum calcium with estimated bone mineral density derived from heel ultrasound in 426 824 individuals who had, on average, calcium levels in the normal range. A fracture genome-wide association metaanalysis comprising 24 cohorts and the UK Biobank including a total of 76 549 cases and 470 164 controls, who, on average, also had calcium levels in the normal range was then performed.

    RESULTS: A standard deviation increase in genetically derived serum calcium (0.13 mmol/L or 0.51 mg/dL) was not associated with increased estimated bone mineral density (0.003 g/cm(2), 95% confidence interval -0.059 to 0.066; P=0.92) or a reduced risk of fractures (odds ratio 1.01, 95% confidence interval 0.89 to 1.15; P=0.85) in inverse-variance weighted mendelian randomisation analyses. Sensitivity analyses did not provide evidence of pleiotropic effects.

    CONCLUSIONS: Genetic predisposition to increased serum calcium levels in individuals with normal calcium levels is not associated with an increase in estimated bone mineral density and does not provide clinically relevant protection against fracture. Whether such predisposition mimics the effect of short term calcium supplementation is not known. Given that the same genetically derived increase in serum calcium is associated with an increased risk of coronary artery disease, widespread calcium supplementation in the general population could provide more risk than benefit.

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  • 13. Chang, Alex R
    et al.
    Grams, Morgan E
    Ballew, Shoshana H
    Bilo, Henk
    Correa, Adolfo
    Evans, Marie
    Gutierrez, Orlando M
    Hosseinpanah, Farhad
    Iseki, Kunitoshi
    Kenealy, Timothy
    Klein, Barbara
    Kronenberg, Florian
    Lee, Brian J
    Li, Yuanying
    Miura, Katsuyuki
    Navaneethan, Sankar D
    Roderick, Paul J
    Valdivielso, Jose M
    Visseren, Frank L J
    Zhang, Luxia
    Gansevoort, Ron T
    Hallan, Stein I
    Levey, Andrew S
    Matsushita, Kunihiro
    Shalev, Varda
    Woodward, Mark
    Ärnlöv, Johan (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lannfelt, Lars (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium2019In: The BMJ, E-ISSN 1756-1833, Vol. 364, article id k5301Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality.

    DESIGN: Individual participant data meta-analysis.

    SETTING: Cohorts from 40 countries with data collected between 1970 and 2017.

    PARTICIPANTS: Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607).

    MAIN OUTCOME MEASURES: GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m2) and all cause mortality.

    RESULTS: Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index.

    CONCLUSIONS: Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR.

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  • 14. Dal-Ré, Rafael
    et al.
    Avendaño-Solà, Cristina
    Bloechl-Daum, Brigitte
    de Boer, Anthonius
    Eriksson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Fuhr, Uwe
    Holm, Søren
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Mentz, Robert J
    Perucca, Emilio
    Rosendaal, Frits R
    Treweek, Shaun
    Low risk pragmatic trials do not always require participants' informed consent2019In: The BMJ, E-ISSN 1756-1833, Vol. 364, article id l1092Article in journal (Other academic)
  • 15.
    Delicano, Rachel Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Egenvall, Agneta
    Westgarth, Carri
    Mubanga, Mwenya
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kennedy, Beatrice
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The shared risk of diabetes between dog and cat owners and their pets: register based cohort study2020In: The BMJ, E-ISSN 1756-1833, Vol. 371, article id m4337Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate whether dog and cat owners and their pets share a risk of developing diabetes.

    DESIGN: Cohort study.

    SETTING: Register based longitudinal study, Sweden.

    PARTICIPANTS: 208 980 owner-dog pairs and 123 566 owner-cat pairs identified during a baseline assessment period (1 January 2004 to 31 December 2006).

    MAIN OUTCOME MEASURES: Type 2 diabetes events in dog and cat owners and diabetes events in their pets, including date of diagnosis during the follow-up period (1 January 2007 to 31 December 2012). Owners with type 2 diabetes were identified by combining information from the National Patient Register, the Cause of Death Register, and the Swedish Prescribed Drug Register. Information on diabetes in the pets was extracted from veterinary care insurance data. Multi-state models were used to assess the hazard ratios with 95% confidence intervals and to adjust for possible shared risk factors, including personal and socioeconomic circumstances.

    RESULTS: The incidence of type 2 diabetes during follow-up was 7.7 cases per 1000 person years at risk in dog owners and 7.9 cases per 1000 person years at risk in cat owners. The incidence of diabetes in the pets was 1.3 cases per 1000 dog years at risk and 2.2 cases per 1000 cat years at risk. The crude hazard ratio for type 2 diabetes in owners of a dog with diabetes compared with owners of a dog without diabetes was 1.38 (95% confidence interval 1.10 to 1.74), with a multivariable adjusted hazard ratio of 1.32 (1.04 to 1.68). Having an owner with type 2 diabetes was associated with an increased hazard of diabetes in the dog (crude hazard ratio 1.28, 1.01 to 1.63), which was attenuated after adjusting for owner's age, with the confidence interval crossing the null (1.11, 0.87 to 1.42). No association was found between type 2 diabetes in cat owners and diabetes in their cats (crude hazard ratio 0.99, 0.74 to 1.34, and 1.00, 0.78 to 1.28, respectively).

    CONCLUSIONS: Data indicated that owners of a dog with diabetes were more likely to develop type 2 diabetes during follow-up than owners of a dog without diabetes. It is possible that dogs with diabetes could serve as a sentinel for shared diabetogenic health behaviours and environmental exposures.

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  • 16.
    Di Giuseppe, Daniela
    et al.
    Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, S-17177 Stockholm, Sweden..
    Alfredsson, Lars
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-17177 Stockholm, Sweden..
    Bottai, Matteo
    Karolinska Inst, Inst Environm Med, Div Biostat, S-17177 Stockholm, Sweden..
    Askling, Johan
    Karolinska Hosp, Dept Med, Clin Epidemiol Unit, S-10401 Stockholm, Sweden..
    Wolk, Alicja
    Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, S-17177 Stockholm, Sweden..
    Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study2012In: The BMJ, E-ISSN 1756-1833, Vol. 345, article id e4230Article in journal (Refereed)
    Abstract [en]

    Objective To analyse the association between alcohol intake and incidence of rheumatoid arthritis in women. Design Prospective cohort study with repeated measurements. Setting The Swedish Mammography Cohort, a population based cohort from central Sweden. Participants 34 141 women born between 1914 and 1948, followed up from 1 January 2003 to 31 December 2009. Main outcome measures Newly diagnosed cases of rheumatoid arthritis identified by linkage with two Swedish national registers. Data on alcohol consumption were collected in 1987 and 1997. Results During the follow-up period (226 032 person years), 197 incident cases of rheumatoid arthritis were identified. There was a statistically significant 37% decrease in risk of rheumatoid arthritis among women who drank >4 glasses of alcohol (1 glass = 15 g of ethanol) per week compared with women who drank <1 glass per week or who never drank alcohol (relative risk 0.63 (95% confidence interval 0.42 to 0.96), P=0.04). Drinking of all types of alcohol (beer, wine, and liquor) was non-significantly inversely associated with the risk of rheumatoid arthritis. Analysis of long term alcohol consumption showed that women who reported drinking >3 glasses of alcohol per week in both 1987 and 1997 had a 52% decreased risk of rheumatoid arthritis compared with those who never drank (relative risk 0.48 (0.24 to 0.98)). Conclusion Moderate consumption of alcohol is associated with reduced risk of rheumatoid arthritis.

  • 17. Di Mario, C.
    et al.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Dudek, D.
    Sabate, M.
    Degertekin, M.
    Commentary: The risk of over-regulation2011In: The BMJ, E-ISSN 1756-1833, Vol. 342, p. d3021-Article in journal (Other academic)
  • 18. Dorlo, Thomas P C
    et al.
    Ravinetto, Raffaella M
    Beijnen, Jos H
    Boelaert, Marleen
    Commentary: Substandard medicines are the priority for neglected tropical diseases.2012In: The BMJ, E-ISSN 1756-1833, Vol. 345, p. e7518-, article id e7518Article in journal (Refereed)
  • 19. Ekstrom, Magnus P.
    et al.
    Bornefalk-Hermansson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Abernethy, Amy P.
    Currow, David C.
    Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study2014In: The BMJ, E-ISSN 1756-1833, Vol. 348, p. g445-Article in journal (Refereed)
    Abstract [en]

    Objective To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD). Design Population based longitudinal consecutive cohort study. Setting Centres prescribing long term oxygen therapy in Sweden. Patients 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register. Main outcome measures Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs. Results 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation. No patient was lost to follow-up. Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively. Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend. Opioids also had a dose response relation with mortality: lower dose opioids (<= 30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44). Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99). Associations were not modified by being naive to the drugs or by hypercapnia. Conclusions Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease.

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  • 20.
    Forsberg, Joanna Stjernschantz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Hansson, Mats G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Eriksson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Biobank Research and Consent: Authors' reply to Sheehan2011In: The BMJ, E-ISSN 1756-1833, Vol. 343, p. d6901-Article in journal (Refereed)
  • 21.
    Gambadauro, Pietro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Magos, Adam
    Pain control in hysteroscopy: Finesse, not local anaesthesia2010In: The BMJ, E-ISSN 1756-1833, Vol. 340, p. c2097-Article in journal (Refereed)
    Abstract
  • 22. Glimåker, Martin
    et al.
    Lindquist, Lars
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Lumbar puncture in adult bacterial meningitis: time to reconsider guidelines?2013In: The BMJ, E-ISSN 1756-1833, Vol. 346, article id f361Article in journal (Refereed)
  • 23.
    Heddini, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    So, Anthony
    Duke University.
    Furlong, Melissa
    Duke University.
    Globalisation and antibiotic resistance2010In: The BMJ, E-ISSN 1756-1833, Vol. 341, p. c5116-Article in journal (Other academic)
  • 24. Heikkila, Katriina
    et al.
    Nyberg, Solja T.
    Theorell, Tores
    Fransson, Eleonor I.
    Alfredsson, Lars
    Bjorner, Jakob B.
    Bonenfant, Sebastien
    Borritz, Marianne
    Bouillon, Kim
    Burr, Herman
    Dragano, Nico
    Geuskens, Goedele A.
    Goldberg, Marcel
    Hamer, Mark
    Hooftman, Wendela E.
    Houtman, Irene L.
    Joensuu, Matti
    Knutsson, Anders
    Koskenvuo, Markku
    Koskinen, Aki
    Kouvonen, Anne
    Madsen, Ida E. H.
    Magnusson, Linda L.
    Marmot, Michael G.
    Nielsen, Martin L.
    Nordin, Maria
    Oksanen, Tuula
    Pentti, Jaana
    Salo, Paula
    Rugulies, Reiner
    Steptoe, Andrew
    Suominen, Sakari
    Vahtera, Jussi
    Virtanen, Marianna
    Vaananen, Ari
    Westerholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Westerlund, Hugo
    Zins, Marie
    Ferrie, Jane E.
    Singh-Manoux, Archana
    Batty, G. David
    Kivimaki, Mika
    Work stress and risk of cancer: meta-analysis of 5700 incident cancer events in 116 000 European men and women2013In: The BMJ, E-ISSN 1756-1833, Vol. 346, p. f165-Article in journal (Refereed)
    Abstract [en]

    Objective To investigate whether work related stress, measured and defined as job strain, is associated with the overall risk of cancer and the risk of colorectal, lung, breast, or prostate cancers. Design Meta-analysis of pooled prospective individual participant data from 12 European cohort studies including 116 056 men and women aged 17-70 who were free from cancer at study baseline and were followed-up for a median of 12 years. Work stress was measured and defined as job strain, which was self reported at baseline. Incident cancers (all n=5765, colorectal cancer n=522, lung cancer n=374, breast cancer n=1010, prostate cancer n=865) were ascertained from cancer, hospital admission, and death registers. Data were analysed in each study with Cox regression and the study specific estimates pooled in meta-analyses. Models were adjusted for age, sex, socioeconomic position, body mass index (BMI), smoking, and alcohol intake Results A harmonised measure of work stress, high job strain, was not associated with overall risk of cancer (hazard ratio 0.97, 95% confidence interval 0.90 to 1.04) in the multivariable adjusted analyses. Similarly, no association was observed between job strain and the risk of colorectal (1.16, 0.90 to 1.48), lung (1.17, 0.88 to 1.54), breast (0.97, 0.82 to 1.14), or prostate (0.86, 0.68 to 1.09) cancers. There was no clear evidence for an association between the categories of job strain and the risk of cancer. Conclusions These findings suggest that work related stress, measured and defined as job strain, at baseline is unlikely to be an important risk factor for colorectal, lung, breast, or prostate cancers.

  • 25.
    Hetland, Merete Lund
    et al.
    Rigshosp, Copenhagen Ctr Arthrit Res COPECARE, Ctr Rheumatol & Spine Dis, Glostrup, Denmark.;Rigshosp, DANBIO, Ctr Rheumatol & Spine Dis, Glostrup, Denmark.;Univ Copenhagen, Dept Clin Med, Fac Hlth Sci, Copenhagen, Denmark..
    Haavardsholm, Espen A.
    Diakonhjemmet Hosp, Dept Rheumatol, Oslo, Norway..
    Rudin, Anna
    Sahlgrens Univ Hosp, Rheumatol Clin, Gothenburg, Sweden.;Univ Gothenburg, Inst Med, Dept Rheumatol & Inflammat Res, Sahlgrenska Acad, Gothenburg, Sweden..
    Nordstrom, Dan
    Helsinki Univ Hosp, Div Rheumatol, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland.;Univ Southern Denmark, Dept Reg Hlth Res, Odense, Denmark..
    Nurmohamed, Michael
    Amsterdam Rheumatol & Immunol Ctr, Reade, Netherlands.;Univ Amsterdam, Dept Rheumatol, Med Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Amsterdam Rheumatol Ctr, Med Ctr, Amsterdam, Netherlands..
    Gudbjornsson, Bjorn
    Landspitali Univ Hosp, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Lampa, Jon
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Horslev-Petersen, Kim
    Univ Hosp Southern Denmark, Danish Hosp Rheumat Dis, Sonderborg, Denmark.;Univ Southern Denmark, Dept Reg Hlth Res, Odense, Denmark..
    Uhlig, Till
    Univ Oslo, Oslo, Norway..
    Grondal, Gerdur
    Landspitali Univ Hosp, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Ostergaard, Mikkel
    Heiberg, Marte S.
    Twisk, Jos
    Univ Amsterdam, Dept Epidemiol & Biostat, Med Ctr, Amsterdam, Netherlands..
    Lend, Kristina
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Krabbe, Simon
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Hyldstrup, Lise Hejl
    Rigshosp, Copenhagen Ctr Arthrit Res COPECARE, Ctr Rheumatol & Spine Dis, Glostrup, Denmark..
    Lindqvist, Joakim
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Ekwall, Anna-Karin Hultgard
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Gron, Kathrine Lederballe
    Kapetanovic, Meliha
    Skane Univ Hosp, Dept Clin Sci Lund, Rheumatol Sect, Lund, Sweden.;Lund Univ, Dept Clin Sci Malmö, Rheumatol, Malmö, Sweden..
    Faustini, Francesca
    Tuompo, Riitta
    Univ Helsinki, Helsinki, Finland..
    Lorenzen, Tove
    Silkeborg Univ Clin, Dept Rheumatol, Silkeborg, Denmark..
    Cagnotto, Giovanni
    Skane Univ Hosp, Dept Rheumatol, Malmö, Sweden.;Lund Univ, Dept Clin Sci Malmö, Rheumatol, Malmö, Sweden.;Jyvaskyla Cent Hosp, Dept Med, Jyvaskyla, Finland.;Univ Eastern Finland, Jyvaskyla Cent Hosp, Jyvaskyla, Finland..
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hendricks, Oliver
    Vedder, Daisy
    Sokka-Isler, Tuulikki
    Jyvaskyla Cent Hosp, Dept Med, Jyvaskyla, Finland..
    Husmark, Tomas
    Univ Eastern Finland, Jyvaskyla Cent Hosp, Jyvaskyla, Finland..
    Ljosa, Maud-Kristine Aga
    Falun Cent Hosp, Dept Rheumatol, Falun, Sweden..
    Brodin, Eli
    Iesund Hosp, Dept Rheumatol, Iesund, Norway..
    Ellingsen, Torkell
    Haukeland Hosp, Dept Rheumatol, Bergen, Norway.;Univ Southern Denmark, Odense Univ Hosp, Rheumatol Res Unit, Odense, Denmark..
    Soderbergh, Annika
    Örebro Univ Hosp, Dept Rheumatol, Örebro, Sweden..
    Rizk, Milad
    Vastmanlands Hosp Västerås, Rheumatol Clin, Västerås, Sweden..
    Olsson, Asa Reckner
    Linköping Univ Hosp, Dept Rheumatol, Linköping, Sweden..
    Larsson, Per
    Acad Specialist Ctr, Stockholm, Sweden..
    Uhrenholt, Line
    Aalborg Univ Hosp, Dept Rheumatol, Aalborg, Denmark..
    Just, Soren Andreas
    Amsterdam Rheumatol & Immunol Ctr, Reade, Netherlands.;Univ Iceland, Fac Med, Reykjavik, Iceland.;Svendborg Hosp OUH, Rheumatol Sect, Dept Med, Svendborg, Denmark..
    Stevens, David John
    Univ Trondheim Hosp, St Olavs Hosp, Dept Rheumatol, Trondheim, Norway..
    Laurberg, Trine Bay
    Aarhus Univ Hosp, Dept Rheumatol, Aarhus, Denmark..
    Bakland, Gunnstein
    Univ Hosp North Norway, Dept Rheumatol, Tromso, Norway..
    Olsen, Inge C.
    Oslo Univ Hosp, Dept Res Support Clin Trials, Oslo, Norway..
    van Vollenhoven, Ronald
    Univ Amsterdam, Dept Rheumatol, Med Ctr, Amsterdam, Netherlands.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial2020In: The BMJ, E-ISSN 1756-1833, Vol. 371, article id m4328Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis.

    DESIGN

    Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study.

    SETTING

    Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018.

    PARTICIPANTS

    Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein.

    INTERVENTIONS

    Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab.

    MAIN OUTCOME MEASURES

    The primary outcome was adjusted clinical disease activity index remission (CDAI <= 2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms.

    RESULTS

    812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms.

    CONCLUSIONS

    All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.

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  • 26.
    Hopkins, Heidi
    et al.
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Bruxvoort, Katia J.
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Cairns, Matthew E.
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Chandler, Clare I. R.
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Leurent, Baptiste
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Ansah, Evelyn K.
    Ghana Hlth Serv, Accra, Ghana..
    Baiden, Frank
    Ensign Coll Publ Hlth, Kpong, Ghana..
    Baltzell, Kimberly A.
    Univ Calif San Francisco, San Francisco, CA 94143 USA..
    Bjorkman, Anders
    Karolinska Inst, S-17176 Stockholm, Sweden..
    Burchett, Helen E. D.
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Clarke, Sian E.
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    DiLiberto, Deborah D.
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Elfving, Kristina
    Univ Gothenburg, Gothenburg, Sweden..
    Goodman, Catherine
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Hansen, Kristian S.
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England.;Univ Copenhagen, DK-1014 Copenhagen, Denmark..
    Kachur, S. Patrick
    US Ctr Dis Control & Prevent, Atlanta, GA USA..
    Lal, Sham
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Lalloo, David G.
    Univ Liverpool Liverpool Sch Trop Med, Liverpool, Merseyside, England..
    Leslie, Toby
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England.;Hlth Protect Res Org, Kabul, Afghanistan..
    Magnussen, Pascal
    Univ Copenhagen, Ctr Med Parasitol, Copenhagen, Denmark.;Univ Copenhagen, Copenhagen Univ Hosp, Copenhagen, Denmark.;Univ Copenhagen, Dept Vet Dis Biol, Copenhagen, Denmark..
    Jefferies, Lindsay Mangham
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Mayan, Ismail
    Hlth Protect Res Org, Kabul, Afghanistan..
    Mbonye, Anthony K.
    Minist Hlth, Kampala, Uganda.;Makerere Univ, Sch Publ Hlth, Kampala, Uganda..
    Msellem, Mwinyi I.
    Zanzibar Malaria Eliminat Programme, Zanzibar, Tanzania..
    Onwujekwe, Obinna E.
    Univ Nigeria, Dept Pharmacol & Therapeut, Enugu, Nigeria..
    Owusu-Agyei, Seth
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England.;Kintampo Hlth Res Ctr, Kintampo, Ghana..
    Reyburn, Hugh
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Rowland, Mark W.
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Shakely, Deler
    Karolinska Inst, Ctr Malaria Res, Stockholm, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Hlth Metr, Gothenburg, Sweden..
    Vestergaard, Lasse S.
    Statens Serum Inst, Dept Infect Dis Epidemiol, Copenhagen, Denmark..
    Webster, Jayne
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Wiseman, Virginia L.
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England.;Univ New South Wales, Sch Publ Hlth & Community Med, Sydney, NSW, Australia..
    Yeung, Shunmay
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Schellenberg, David
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Staedke, Sarah G.
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Whitty, Christopher J. M.
    Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England..
    Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings2017In: The BMJ, E-ISSN 1756-1833, Vol. 356, article id j1054Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia. DESIGN Analysis of nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study). SETTING Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda. PARTICIPANTS 522 480 children and adults with acute febrile illness. INTERVENTIONS Rapid diagnostic tests for malaria. MAIN OUTCOME MEASURES Proportions of patients for whom an antibiotic was prescribed in trial groups who had undergone rapid diagnostic testing compared with controls and in patients with negative test results compared with patients with positive results. A secondary aim compared classes of antibiotics prescribed in different settings. RESULTS Antibiotics were prescribed to 127 052/238 797 (53%) patients in control groups and 167 714/283 683 (59%) patients in intervention groups. Antibiotics were prescribed to 40% (35 505/89 719) of patients with a positive test result for malaria and to 69% (39 400/57 080) of those with a negative result. All but one study showed a trend toward more antibiotic prescribing in groups who underwent rapid diagnostic tests. Random effects meta-analysis of the trials showed that the overall risk of antibiotic prescription was 21% higher (95% confidence interval 7% to 36%) in intervention settings. In most intervention settings, patients with negative test results received more antibiotic prescriptions than patients with positive results for all the most commonly used classes: penicillins, trimethoprim-sulfamethoxazole (one exception), tetracyclines, and metronidazole. CONCLUSIONS Introduction of rapid diagnostic tests for malaria to reduce unnecessary use of antimalarials-a beneficial public health outcome-could drive up untargeted use of antibiotics. That 69% of patients were prescribed antibiotics when test results were negative probably represents overprescription. This included antibiotics from several classes, including those like metronidazole that are seldom appropriate for febrile illness, across varied clinical, health system, and epidemiological settings. It is often assumed that better disease specific diagnostics will reduce antimicrobial overuse, but they might simply shift it from one antimicrobial class to another. Current global implementation of malaria testing might increase untargeted antibiotic use and must be examined.

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  • 27.
    Hägglund, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    DesRoches, Catherine
    Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
    Petersen, Carolyn
    Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
    Scandurra, Isabella
    Informatics, Örebro University School of Business, Örebro, Sweden.
    Patients’ access to health records2019In: The BMJ, E-ISSN 1756-1833, Vol. 367, article id l5725Article in journal (Other academic)
    Abstract [en]

    Patients and clinicians are equally frustrated by the slow pace of changeThe international movement pushing to increase transparency by giving patients easy access to their health information parallels a broader shift in healthcare towards increased patient empowerment and participation. In the United States, the philanthropic OpenNotes initiative works to increase transparency by encouraging healthcare organisations to provide patients with access to notes in their electronic health record. It began in 2010 as a pilot that included 105 volunteer primary care providers and their 19 000 patients and has since spread throughout the US, with more than 200 organisations offering roughly 41 million patients access to their clinical notes. In Sweden, the first region-wide implementation of patient access to electronic health records was in 2012, more than 10 years after the first pilot study. All 21 Swedish regions have now offered this e-service through a national patient portal that integrates with all electronic health record systems currently used in Sweden. More than 3 million people (>30% of the population) had accessed their records online by August 2019, and more than 2 million logins occur each month.

    Similar patient accessible electronic record systems are implemented in other countries, though different strategies and approaches have influenced uptake and impact. Progress has been slow because of legal constraints, technical challenges, and concerns or resistance among healthcare professionals. Low rates of adoption among patients have also been a problem in some areas. Nonetheless, research evidence reports positive outcomes among patients accessing their records, and the concerns expressed by healthcare professionals have not been realised. Patients who read their notes report understanding their care plans better, feeling more in control of their care, doing a better job taking their medications, improved communication with and trust in their clinicians, and improved patient safety.

  • 28. Hägglund, Maria
    et al.
    Koch, Sabine
    Commentary: Sweden rolls out online access to medical records and is developing new e-health services to enable people to manage their care.2015In: The BMJ, E-ISSN 1756-1833, Vol. 350, article id h359Article in journal (Refereed)
  • 29.
    Högberg, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research.
    Squir, Waney
    Thiblin, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Fellman, Vineta
    Högberg, Göran
    Andersson, Jacob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Wester, Knut
    Preventable harm and child maltreatment diagnosis (eLetter)2019In: The BMJ, E-ISSN 1756-1833, Vol. 366Article in journal (Refereed)
    Abstract [en]

    Objective: To systematically quantify the prevalence, severity, and nature of preventable patient harm across a range of medical settings globally.

    Design: Systematic review and meta-analysis.

    Data sources: Medline, PubMed, PsycINFO, Cinahl and Embase, WHOLIS, Google Scholar, and SIGLE from January 2000 to January 2019. The reference lists of eligible studies and other relevant systematic reviews were also searched.

    Review methods: Observational studies reporting preventable patient harm in medical care. The core outcomes were the prevalence, severity, and types of preventable patient harm reported as percentages and their 95% confidence intervals. Data extraction and critical appraisal were undertaken by two reviewers working independently. Random effects meta-analysis was employed followed by univariable and multivariable meta regression. Heterogeneity was quantified by using the I2 statistic, and publication bias was evaluated.

    Results: Of the 7313 records identified, 70 studies involving 337 025 patients were included in the meta-analysis. The pooled prevalence for preventable patient harm was 6% (95% confidence interval 5% to 7%). A pooled proportion of 12% (9% to 15%) of preventable patient harm was severe or led to death. Incidents related to drugs (25%, 95% confidence interval 16% to 34%) and other treatments (24%, 21% to 30%) accounted for the largest proportion of preventable patient harm. Compared with general hospitals (where most evidence originated), preventable patient harm was more prevalent in advanced specialties (intensive care or surgery; regression coefficient b=0.07, 95% confidence interval 0.04 to 0.10).

    Conclusions: Around one in 20 patients are exposed to preventable harm in medical care. Although a focus on preventable patient harm has been encouraged by the international patient safety policy agenda, there are limited quality improvement practices specifically targeting incidents of preventable patient harm rather than overall patient harm (preventable and non-preventable). Developing and implementing evidence-based mitigation strategies specifically targeting preventable patient harm could lead to major service quality improvements in medical care which could also be more cost effective.

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  • 30.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Enoxaparin for anticoagulation in patients undergoing percutaneous coronary intervention2012In: The BMJ, E-ISSN 1756-1833, Vol. 344, p. e712-Article in journal (Refereed)
  • 31.
    James, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Daubert, Jean-Claude
    Van de Werf, Frans
    Commentary: Use of registries to investigate the past and develop the future2011In: The BMJ, E-ISSN 1756-1833, Vol. 342, p. d2826-Article in journal (Other academic)
  • 32.
    James, Stefan K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Roe, Matthew T.
    Cannon, Christopher P.
    Cornel, Jan H.
    Horrow, Jay
    Husted, Steen
    Katus, Hugo
    Morais, Joao
    Steg, Ph Gabriel
    Storey, Robert F.
    Stevens, Susanna
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Harrington, Robert A.
    Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial2011In: The BMJ, E-ISSN 1756-1833, Vol. 342, p. d3527-Article in journal (Refereed)
    Abstract [en]

    Objective To evaluate efficacy and safety outcomes in patients in the PLATelet inhibition and patient Outcomes (PLATO) trial who at randomisation were planned for a non-invasive treatment strategy. Design Pre-specified analysis of pre-randomisation defined subgroup of prospective randomised clinical trial. Setting 862 centres in 43 countries. Participants 5216 (28%) of 18 624 patients admitted to hospital for acute coronary syndrome who were specified as planned for non-invasive management. Interventions Randomised treatment with ticagrelor (n=2601) versus clopidogrel (2615). Main outcome measurements Primary composite end point of cardiovascular death, myocardial infarction, and stroke; their individual components; and PLATO defined major bleeding during one year. Results 2183 (41.9%) patients had coronary angiography during their initial hospital admission, 1065 (20.4%) had percutaneous coronary intervention, and 208 (4.0%) had coronary artery bypass surgery. Cumulatively, 3143 (60.3%) patients had been managed non-invasively by the end of follow-up. The incidence of the primary end point was lower with ticagrelor than with clopidogrel (12.0% (n=295) v 14.3% (346); hazard ratio 0.85, 95% confidence interval 0.73 to 1.00; P=0.04). Overall mortality was also lower (6.1% (147) v 8.2% (195); 0.75, 0.61 to 0.93; P=0.01). The incidence of total major bleeding (11.9% (272) v 10.3% (238); 1.17, 0.98 to 1.39; P=0.08) and non-coronary artery bypass grafting related major bleeding (4.0% (90) v 3.1% (71); 1.30, 0.95 to 1.77; P=0.10) was numerically higher with ticagrelor than with clopidogrel. Conclusions In patients with acute coronary syndrome initially intended for non-invasive management, the benefits of ticagrelor over clopidogrel were consistent with those from the overall PLATO results, indicating the broad benefits of P2Y12 inhibition with ticagrelor regardless of intended management strategy.

  • 33.
    Janson, Christer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Larsson, Kjell
    Lisspers, Karin H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Ställberg, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Stratelis, Georgios
    Goike, Helena
    Jorgensen, Leif
    Johansson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting beta(2) agonist: observational matched cohort study (PATHOS)2013In: The BMJ, E-ISSN 1756-1833, Vol. 346, p. f3306-Article in journal (Refereed)
    Abstract [en]

    Objective To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting beta(2) agonist. Design Observational retrospective pairwise cohort study matched (1:1) for propensity score. Setting Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009. Participants Patients with COPD diagnosed by a physician and prescriptions of either budesonide/formoterol or fluticasone/salmeterol. Main outcome measures Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality. Results 9893 patients were eligible for matching (2738 in the fluticasone/salmeterol group; 7155 in the budesonide/formoterol group), yielding two matched cohorts of 2734 patients each. In these patients, 2115 (39%) had at least one recorded episode of pneumonia during the study period, with 2746 episodes recorded during 19 170 patient years of follow up. Compared with budesonide/formoterol, rate of pneumonia and admission to hospital were higher in patients treated with fluticasone/salmeterol:rate ratio 1.73 (95% confidence interval 1.57 to 1.90; P<0.001) and 1.74 (1.56 to 1.94; P<0.001), respectively. The pneumonia event rate per 100 patient years for fluticasone/salmeterol versus budesonide/formoterol was 11.0 (10.4 to 11.8) versus 6.4 (6.0 to 6.9) and the rate of admission to hospital was 7.4 (6.9 to 8.0) versus 4.3 (3.9 to 4.6). The mean duration of admissions related to pneumonia was similar for both groups, but mortality related to pneumonia was higher in the fluticasone/salmeterol group (97 deaths) than in the budesonide/formoterol group (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003). All cause mortality did not differ between the treatments (1.08, 0.93 to 1.14; P=0.59). Conclusions There is an intra-class difference between fixed combinations of inhaled corticosteroid/long acting beta(2) agonist with regard to the risk of pneumonia and pneumonia related events in the treatment of patients with COPD. Trial registration Clinical Trials.gov NCT01146392.

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  • 34.
    Johansson, Emily White
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Hildenwall, Helena
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Dept Paediat, Solna, Sweden.
    Nsona, Humphreys
    Integrated Management Childhood Illness IMCI, Lilongwe, Malawi.
    de Lauwerier, Valentina Buj
    United Nations Childrens Fund, New York, NY USA.
    Peterson, Stefan Swartling
    United Nations Childrens Fund, New York, NY USA.
    Rapid diagnostic tests for malaria: Do rapid diagnostic tests improve overall quality of care?2017In: The BMJ, E-ISSN 1756-1833, Vol. 357, article id j2290Article in journal (Other academic)
  • 35.
    Kivimaki, Mika
    et al.
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England;Univ Helsinki, Clinicum, Fac Med, FI-00014 Helsinki, Finland;Univ Helsinki, Helsinki Inst Life Sci, Helsinki, Finland.
    Singh-Manoux, Archana
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England;INSERM, U1153, Epidemiol Ageing & Neurodegenerat Dis, Paris, France.
    Pentti, Jaana
    Univ Helsinki, Clinicum, Fac Med, FI-00014 Helsinki, Finland;Univ Turku, Dept Publ Hlth, Turku, Finland.
    Sabia, Severine
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England;INSERM, U1153, Epidemiol Ageing & Neurodegenerat Dis, Paris, France.
    Nyberg, Solja T.
    Univ Helsinki, Clinicum, Fac Med, FI-00014 Helsinki, Finland.
    Alfredsson, Lars
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Goldberg, Marcel
    INSERM, UMS 011, Populat Based Epidemiol Cohorts Unit, Villejuif, France.
    Knutsson, Anders
    Mid Sweden Univ, Dept Hlth Sci, Sundsvall, Sweden.
    Koskenvuo, Markku
    Univ Helsinki, Clinicum, Fac Med, FI-00014 Helsinki, Finland.
    Koskinen, Aki
    Finnish Inst Occupat Hlth, Helsinki, Finland.
    Kouvonen, Anne
    Univ Helsinki, Fac Social Sci, Helsinki, Finland;SWPS Univ Social Sci & Humanities Wroclaw, Wroclaw, Poland;Queens Univ Belfast, Ctr Publ Hlth, Adm Data Res Ctr Northern Ireland, Belfast, Antrim, North Ireland.
    Nordin, Maria
    Stockholm Univ, Stress Res Inst, Stockholm, Sweden;Umea Univ, Dept Psychol, Umea, Sweden.
    Oksanen, Tuula
    Finnish Inst Occupat Hlth, Helsinki, Finland.
    Strandberg, Timo
    Univ Helsinki, Clinicum, Fac Med, FI-00014 Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland;Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland.
    Suominen, Sakari B.
    Univ Turku, Dept Publ Hlth, Turku, Finland;Univ Skovde, Skovde, Sweden.
    Theorell, Tores
    Stockholm Univ, Stress Res Inst, Stockholm, Sweden.
    Vahtera, Jussi
    Univ Turku, Dept Publ Hlth, Turku, Finland;Turku Univ Hosp, Turku, Finland.
    Vaananen, Ari
    Finnish Inst Occupat Hlth, Helsinki, Finland.
    Virtanen, Marianna
    Univ Eastern Finland, Sch Educ Sci & Psychol, Joensuu, Finland.
    Westerholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Westerlund, Hugo
    Stockholm Univ, Stress Res Inst, Stockholm, Sweden.
    Zins, Marie
    INSERM, UMS 011, Populat Based Epidemiol Cohorts Unit, Villejuif, France.
    Seshadri, Sudha
    Univ Texas Hlth Sci Ctr San Antonio, Glenn Biggs Inst Alzheimers & Neurodegenerat Dis, San Antonio, TX 78229 USA;Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
    Batty, G. David
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
    Sipila, Pyry N.
    Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England.
    Shipley, Martin J.
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
    Lindbohm, Joni V.
    Univ Helsinki, Clinicum, Fac Med, FI-00014 Helsinki, Finland.
    Ferrie, Jane E.
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England;Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England.
    Jokela, Markus
    Univ Helsinki, Biomedicum, Fac Med, Helsinki, Finland.
    Physical inactivity, cardiometabolic disease, and risk of dementia: an individual-participant meta-analysis2019In: The BMJ, E-ISSN 1756-1833, Vol. 365, article id l1495Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To examine whether physical inactivity is a risk factor for dementia, with attention to the role of cardiometabolic disease in this association and reverse causation bias that arises from changes in physical activity in the preclinical (prodromal) phase of dementia. DESIGN Meta-analysis of 19 prospective observational cohort studies. DATA SOURCES The Individual-Participant-Data Meta-analysis in Working Populations Consortium, the Inter-University Consortium for Political and Social Research, and the UK Data Service, including a total of 19 of a potential 9741 studies. REVIEW METHOD The search strategy was designed to retrieve individual-participant data from prospective cohort studies. Exposure was physical inactivity; primary outcomes were incident all-cause dementia and Alzheimer's disease; and the secondary outcome was incident cardiometabolic disease (that is, diabetes, coronary heart disease, and stroke). Summary estimates were obtained using random effects meta-analysis. RESULTS Study population included 404 840 people (mean age 45.5 years, 57.7% women) who were initially free of dementia, had a measurement of physical inactivity at study entry, and were linked to electronic health records. In 6.0 million person-years at risk, we recorded 2044 incident cases of all-cause dementia. In studies with data on dementia subtype, the number of incident cases of Alzheimer's disease was 1602 in 5.2 million person-years. When measured < 10 years before dementia diagnosis (that is, the preclinical stage of dementia), physical inactivity was associated with increased incidence of all-cause dementia (hazard ratio 1.40, 95% confidence interval 1.23 to 1.71) and Alzheimer's disease (1.36, 1.12 to 1.65). When reverse causation was minimised by assessing physical activity >= 10 years before dementia onset, no difference in dementia risk between physically active and inactive participants was observed (hazard ratios 1.01 (0.89 to 1.14) and 0.96 (0.85 to 1.08) for the two outcomes). Physical inactivity was consistently associated with increased risk of incident diabetes (hazard ratio 1.42, 1.25 to 1.61), coronary heart disease (1.24, 1.13 to 1.36), and stroke (1.16, 1.05 to 1.27). Among people in whom cardiometabolic disease preceded dementia, physical inactivity was non-significantly associated with dementia (hazard ratio for physical activity assessed > 10 before dementia onset 1.30, 0.79 to 2.14). CONCLUSIONS In analyses that addressed bias due to reverse causation, physical inactivity was not associated with all-cause dementia or Alzheimer's disease, although an indication of excess dementia risk was observed in a subgroup of physically inactive individuals who developed cardiometabolic disease.

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  • 36.
    Kivimaki, Mika
    et al.
    UCL, Dept Epidemiol & Publ Hlth, London, England.;Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland.;Finnish Inst Occupat Hlth, Helsinki, Finland..
    Walker, Keenan A.
    Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.;NIA, Lab Behav Neurosci, Intramural Res Program, Baltimore, MD 21224 USA..
    Pentti, Jaana
    Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland.;Finnish Inst Occupat Hlth, Helsinki, Finland.;Univ Turku, Dept Publ Hlth, Turku, Finland..
    Nyberg, Solja
    Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland..
    Mars, Nina
    Univ Helsinki, Inst Mol Med Finland, HiLIFE, Helsinki, Finland..
    Vahtera, Jussi
    Univ Turku, Dept Publ Hlth, Turku, Finland.;Univ Turku, Ctr Populat Hlth Res, Turku, Finland.;Turku Univ Hosp, Turku, Finland..
    Suominen, Sakari B.
    Univ Turku, Dept Publ Hlth, Turku, Finland.;Univ Skövde, Sch Hlth Sci, Skövde, Sweden..
    Lallukka, Tea
    Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland..
    Rahkonen, Ossi
    Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland..
    Pietilainen, Olli
    Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland..
    Koskinen, Aki
    Finnish Inst Occupat Hlth, Helsinki, Finland..
    Vaananen, Ari
    Finnish Inst Occupat Hlth, Helsinki, Finland..
    Kalsi, Jatinderpal K.
    UCL, Dept Epidemiol & Publ Hlth, London, England..
    Goldberg, Marcel
    INSERM, UMS 011, Populat Based Epidemiol Cohorts Unit, Villejuif, France.;Univ Paris, INSERM U1153, Epidemiol Ageing & Neurodegenerat Dis, Paris, France..
    Zins, Marie
    INSERM, UMS 011, Populat Based Epidemiol Cohorts Unit, Villejuif, France.;Univ Paris, INSERM U1153, Epidemiol Ageing & Neurodegenerat Dis, Paris, France..
    Alfredsson, Lars
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Reg Stockholm, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Westerholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine. Uppsala Univ, Dept Med Sci, Uppsala, Sweden..
    Knutsson, Anders
    Mid Sweden Univ, Dept Hlth Sci, Sundsvall, Sweden..
    Theorell, Tores
    Stockholm Univ, Stress Res Inst, Stockholm, Sweden..
    Ervasti, Jenni
    Finnish Inst Occupat Hlth, Helsinki, Finland..
    Oksanen, Tuula
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Sipila, Pyry N.
    Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland..
    Tabak, Adam G.
    UCL, Dept Epidemiol & Publ Hlth, London, England.;Semmelweis Univ, Dept Internal Med & Oncol, Budapest, Hungary.;Semmelweis Univ, Dept Publ Hlth, Budapest, Hungary..
    Ferrie, Jane E.
    UCL, Dept Epidemiol & Publ Hlth, London, England.;Univ Bristol, Bristol Med Sch, Bristol, Avon, England..
    Williams, Stephen A.
    SomaLogic, Boulder, CO USA..
    Livingston, Gill
    UCL, Div Psychiat, London, England.;Camden & Islington NHS Fdn Trust, London, England..
    Gottesman, Rebecca F.
    Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA..
    Singh-Manoux, Archana
    UCL, Dept Epidemiol & Publ Hlth, London, England.;Univ Paris, INSERM U1153, Epidemiol Ageing & Neurodegenerat Dis, Paris, France..
    Zetterberg, Henrik
    UCL, Dept Neurodegenerat Dis, London, England.;UCL, UK Dementia Res Inst, London, England.;Univ Gothenburg, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Sahlgrenska Acad, Mölndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Mölndal, Sweden..
    Lindbohm, Joni, V
    UCL, Dept Epidemiol & Publ Hlth, London, England.;Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland..
    Cognitive stimulation in the workplace, plasma proteins, and risk of dementia: three analyses of population cohort studies2021In: The BMJ, E-ISSN 1756-1833, Vol. 374, article id 374:n1804Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES To examine the association between cognitively stimulating work and subsequent risk of dementia and to identify protein pathways for this association. DESIGN Multicohort study with three sets of analyses. SETTING United Kingdom, Europe, and the United States. PARTICIPANTS Three associations were examined: cognitive stimulation and dementia risk in 107 896 participants from seven population based prospective cohort studies from the IPD-Work consortium (individual participant data meta-analysis in working populations); cognitive stimulation and proteins in a random sample of 2261 participants from one cohort study; and proteins and dementia risk in 13 656 participants from two cohort studies. MAIN OUTCOME MEASURES Cognitive stimulation was measured at baseline using standard questionnaire instruments on active versus passive jobs and at baseline and over time using a job exposure matrix indicator. 4953 proteins in plasma samples were scanned. Follow-up of incident dementia varied between 13.7 to 30.1 years depending on the cohort. People with dementia were identified through linked electronic health records and repeated clinical examinations. RESULTS During 1.8 million person years at risk, 1143 people with dementia were recorded. The risk of dementia was found to be lower for participants with high compared with low cognitive stimulation at work (crude incidence of dementia per 10 000 person years 4.8 in the high stimulation group and 7.3 in the low stimulation group, age and sex adjusted hazard ratio 0.77, 95% confidence interval 0.65 to 0.92, heterogeneity in cohort specific estimates I2=0%, P=0.99). This association was robust to additional adjustment for education, risk factors for dementia in adulthood (smoking, heavy alcohol consumption, physical inactivity, job strain, obesity, hypertension, and prevalent diabetes at baseline), and cardiometabolic diseases (diabetes, coronary heart disease, stroke) before dementia diagnosis (fully adjusted hazard ratio 0.82, 95% confidence interval 0.68 to 0.98). The risk of dementia was also observed during the first 10 years of follow-up (hazard ratio 0.60, 95% confidence interval 0.37 to 0.95) and from year 10 onwards (0.79, 0.66 to 0.95) and replicated using a repeated job exposure matrix indicator of cognitive stimulation (hazard ratio per 1 standard deviation increase 0.77, 95% confidence interval 0.69 to 0.86). In analysis controlling for multiple testing, higher cognitive stimulation at work was associated with lower levels of proteins that inhibit central nervous system axonogenesis and synaptogenesis: slit homologue 2 (SLIT2, fully adjusted r3 -0.34, P(0.001), carbohydrate sulfotransferase 12 (CHSTC, fully adjusted r3 -0.33, P(0.001), and peptidyl-glycine alpha-amidating monooxygenase (AMD, fully adjusted r3 -0.32, P(0.001). These proteins were associated with increased dementia risk, with the fully adjusted hazard ratio per 1 SD being 1.16 (95% confidence interval 1.05 to 1.28) for SLIT2, 1.13 (1.00 to 1.27) for CHSTC, and 1.04 (0.97 to 1.13) for AMD. CONCLUSIONS The risk of dementia in old age was found to be lower in people with cognitively stimulating jobs than in those with non-stimulating jobs. The findings that

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  • 37.
    Larsson, Susanna C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Traylor, Matthew
    Malik, Rainer
    Dichgans, Martin
    Burgess, Stephen
    Markus, Hugh S
    Modifiable pathways in Alzheimer's disease: Mendelian randomisation analysis.2017In: The BMJ, E-ISSN 1756-1833, Vol. 359, article id j5375Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine which potentially modifiable risk factors, including socioeconomic, lifestyle/dietary, cardiometabolic, and inflammatory factors, are associated with Alzheimer's disease.

    DESIGN: Mendelian randomisation study using genetic variants associated with the modifiable risk factors as instrumental variables.

    SETTING: International Genomics of Alzheimer's Project.

    PARTICIPANTS: 17 008 cases of Alzheimer's disease and 37 154 controls.

    MAIN OUTCOME MEASURES: Odds ratio of Alzheimer's per genetically predicted increase in each modifiable risk factor estimated with Mendelian randomisation analysis.

    RESULTS: This study included analyses of 24 potentially modifiable risk factors. A Bonferroni corrected threshold of P=0.002 was considered to be significant, and P<0.05 was considered suggestive of evidence for a potential association. Genetically predicted educational attainment was significantly associated with Alzheimer's. The odds ratios were 0.89 (95% confidence interval 0.84 to 0.93; P=2.4×10-6) per year of education completed and 0.74 (0.63 to 0.86; P=8.0×10-5) per unit increase in log odds of having completed college/university. The correlated trait intelligence had a suggestive association with Alzheimer's (per genetically predicted 1 SD higher intelligence: 0.73, 0.57 to 0.93; P=0.01). There was suggestive evidence for potential associations between genetically predicted higher quantity of smoking (per 10 cigarettes a day: 0.69, 0.49 to 0.99; P=0.04) and 25-hydroxyvitamin D concentrations (per 20% higher levels: 0.92, 0.85 to 0.98; P=0.01) and lower odds of Alzheimer's and between higher coffee consumption (per one cup a day: 1.26, 1.05 to 1.51; P=0.01) and higher odds of Alzheimer's. Genetically predicted alcohol consumption, serum folate, serum vitamin B12, homocysteine, cardiometabolic factors, and C reactive protein were not associated with Alzheimer's disease.

    CONCLUSION: These results provide support that higher educational attainment is associated with a reduced risk of Alzheimer's disease.

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  • 38.
    Lei, Jiayao
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
    Andrae, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm.
    Ploner, Alexander
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
    Lagheden, Camilla
    Karolinska Inst, Dept Lab Med, S-14183 Stockholm, Sweden.
    Eklund, Carina
    Karolinska Inst, Dept Lab Med, S-14183 Stockholm, Sweden.
    Kleppe, Sara Nordqvist
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden;Karolinska Inst, Dept Lab Med, S-14183 Stockholm, Sweden.
    Wang, Jiangrong
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden;Karolinska Inst, Dept Lab Med, S-14183 Stockholm, Sweden.
    Fang, Fang
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
    Dillner, Joakim
    Karolinska Inst, Dept Lab Med, S-14183 Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Univ Lab, S-17176 Stockholm, Sweden.
    Elfstrom, K. Miriam
    Karolinska Inst, Dept Lab Med, S-14183 Stockholm, Sweden;Reg Canc Ctr Stockholm Gotland, S-11827 Stockholm, Sweden.
    Sparen, Par
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
    Cervical screening and risk of adenosquamous and rare histological types of invasive cervical carcinoma: population based nested case-control study2019In: The BMJ, E-ISSN 1756-1833, Vol. 365, article id l1207Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES

    To examine the association of cervical cytology screening with the risk of adenosquamous cell carcinoma (ASC) and rare histological types of invasive cervical carcinoma (RICC), using comprehensive registry data, and to assess tumour human papillomavirus status of ASC and RICC.

    DESIGN

    Nationwide, population based, nested case-control study.

    SETTING

    Sweden.

    PARTICIPANTS

    All cases of invasive cervical carcinoma in Sweden during 2002-11 (4254 confirmed cases after clinical and histopathological review). 338 cases were neither squamous cell carcinoma nor adenocarcinoma, including 164 cases of ASC and 174 cases of RICC (glassy cell carcinoma, clear cell carcinoma, small cell carcinoma, neuroendocrine cell carcinoma, large cell carcinoma, and undifferentiated carcinoma). 30 birth year matched controls from the general Swedish population were matched to each case by applying incidence density sampling.

    MAIN OUTCOME MEASURES

    Conditional logistic regression was used to calculate odds ratios, interpreted as incidence rate ratios, for risk of ASC and RICC in relation to screening status and screening history, adjusted for education. Human papillomavirus distribution of ASC and RICC was based on available archival tumour tissues from most Swedish pathology biobanks.

    RESULTS

    Women with two screening tests in the previous two recommended screening intervals had a lower risk of ASC (incidence rate ratio 0.22, 95% confidence interval 0.14 to 0.34) and RICC (0.34, 0.21 to 0.55), compared with women without any test. High risk human papillomavirus was detected in 148/211 (70%) cases with valid human papillomavirus results from tumour tissues. The risk reduction among women with tumours that were positive (incidence rate ratio 0.28, 0.18 to 0.46) and negative (0.27, 0.13 to 0.59) for high risk human papillomavirus was similar, compared with women who did not attend any test.

    CONCLUSIONS

    Cervical screening is associated with reduced risk of ASC and RICC, and most ASC and RICC are positive for high risk human papillomavirus. This evidence provides a benchmark for evaluating future cervical screening strategies.

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  • 39.
    Marklund, Matti
    et al.
    The George Institute for Global Health.
    Singh, Gitanjali
    Greer, Raquel
    Cudhea, Frederick
    Matsushita, Kunihiro
    Micha, Renata
    Brady, Tammy
    Zhao, Di
    Huang, Liping
    Tian, Maoyi
    Cobb, Laura
    Neal, Bruce
    Appel, Lawrence J
    Mozaffarian, Dariush
    Wu, Jason H Y
    Estimated population wide benefits and risks in China of lowering sodium through potassium enriched salt substitution: modelling study2020In: The BMJ, E-ISSN 1756-1833, Vol. 369, article id m824Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To estimate the effects of nationwide replacement of discretionary salt (used at table or during cooking) with potassium enriched salt substitute on morbidity and death from cardiovascular disease in China.

    DESIGN: Modelling study.

    SETTING: China.

    POPULATION: Adult population in China, and specifically individuals with chronic kidney disease (about 17 million people).

    INTERVENTIONS: Comparative risk assessment models were used to estimate the effects of a nationwide intervention to replace discretionary dietary salt with potassium enriched salt substitutes (20-30% potassium chloride). The models incorporated existing data and corresponding uncertainties from randomised trials, the China National Survey of Chronic Kidney Disease, the Global Burden of Disease Study, and the Chronic Kidney Disease Prognosis Consortium.

    MAIN OUTCOME MEASURES: Averted deaths from cardiovascular disease, non-fatal events, and disability adjusted life years from a reduction in blood pressure were estimated after implementation of potassium enriched salt substitution. In individuals with chronic kidney disease, additional deaths from cardiovascular disease related to hyperkalaemia from increased intake of potassium were calculated. The net effects on deaths from cardiovascular disease were estimated as the difference and ratio of averted and additional deaths from cardiovascular disease.

    RESULTS: Nationwide implementation of potassium enriched salt substitution could prevent about 461 000 (95% uncertainty interval 196 339 to 704 438) deaths annually from cardiovascular disease, corresponding to 11.0% (4.7% to 16.8%) of annual deaths from cardiovascular disease in China; 743 000 (305 803 to 1 273 098) non-fatal cardiovascular events annually; and 7.9 (3.3 to 12.9) million disability adjusted life years related to cardiovascular disease annually. The intervention could potentially produce an estimated 11 000 (6422 to 16 562) additional deaths related to hyperkalaemia in individuals with chronic kidney disease. The net effect would be about 450 000 (183 699 to 697 084) fewer deaths annually from cardiovascular disease in the overall population and 21 000 (1928 to 42 926) fewer deaths in individuals with chronic kidney disease. In deterministic sensitivity analyses, with changes to key model inputs and assumptions, net benefits were consistent in the total population and in individuals with chronic kidney disease, with averted deaths outweighing additional deaths.

    CONCLUSIONS: Nationwide potassium enriched salt substitution in China was estimated to result in a substantial net benefit, preventing around one in nine deaths from cardiovascular disease overall. Taking account of the risks of hyperkalaemia, a substantial net benefit was also estimated for individuals with chronic kidney disease.

  • 40.
    McCracken, Lance M.
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Yu, Lin
    Middlesex Univ, Dept Psychol, London, England..
    Vowles, Kevin E.
    Queens Univ Belfast, Sch Psychol, Belfast, Antrim, North Ireland..
    New generation psychological treatments in chronic pain2022In: The BMJ, E-ISSN 1756-1833, Vol. 376, article id e057212Article, review/survey (Refereed)
    Abstract [en]

    Chronic pain conditions are common and have a considerable impact on health and wellbeing. This impact can be reduced by cognitive behavioral therapy (CBT), the most commonly applied psychological approach to chronic pain. At the same time, CBT continues to develop, and now includes what is sometimes called "third wave" CBT. In this review, we examine the evidence for application of acceptance and commitment therapy (ACT), a principal example of this new wave or latest generation of treatment approaches, in people with chronic pain. We identified 25 randomized controlled trials of ACT for adults with chronic pain. Across the included trials, small to large effect sizes favoring ACT were reported for key outcomes including pain interference, disability, depression, and quality of life. Evidence from three studies provided some support for the cost effectiveness of ACT for chronic pain. Evidence also supported the mediating role of theoretically consistent processes of change (psychological flexibility) in relation to treatment outcomes. Investigation of moderators and predictors of outcomes was limited and inconsistent. In future, a greater focus on process based treatments is recommended. This should include continued identification of evidence based processes of change, and research methods more suited to understanding the experience and needs of individual people.

  • 41.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Surgeon volume and early complications after primary total hip arthroplasty: Surgeons who do at least 35 procedures a year seem safer than surgeons who do fewer2014In: The BMJ, E-ISSN 1756-1833, Vol. 348, article id g3433Article in journal (Refereed)
  • 42.
    Michaëlsson, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Warensjö Lemming, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wolk, Alicja
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study2013In: The BMJ, E-ISSN 1756-1833, Vol. 346, article id f228Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate the association between long term intake of dietary and supplemental calcium and death from all causes and cardiovascular disease.

    DESIGN:

    Prospective longitudinal cohort study.

    SETTING:

    Swedish mammography cohort, a population based cohort established in 1987-90.

    PARTICIPANTS:

    61 433 women (born between 1914 and 1948) followed-up for a median of 19 years.

    MAIN OUTCOME MEASURES:

    Primary outcome measures, identified from registry data, were time to death from all causes (n=11 944) and cause specific cardiovascular disease (n=3862), ischaemic heart disease (n=1932), and stroke (n=1100). Diet was assessed by food frequency questionnaires at baseline and in 1997 for 38 984 women, and intakes of calcium were estimated. Total calcium intake was the sum of dietary and supplemental calcium.

    RESULTS:

    The risk patterns with dietary calcium intake were non-linear, with higher rates concentrated around the highest intakes (≥1400 mg/day). Compared with intakes between 600 and 1000 mg/day, intakes above 1400 mg/day were associated with higher death rates from all causes (hazard ratio 1.40, 95% confidence interval 1.17 to 1.67), cardiovascular disease (1 49, 1.09 to 2.02), and ischaemic heart disease (2.14, 1.48 to 3.09) but not from stroke (0.73, 0.33 to 1.65). After sensitivity analysis including marginal structural models, the higher death rate with low dietary calcium intake (<600 mg/day) or with low and high total calcium intake was no longer apparent. Use of calcium tablets (6% users; 500 mg calcium per tablet) was not on average associated with all cause or cause specific mortality but among calcium tablet users with a dietary calcium intake above 1400 mg/day the hazard ratio for all cause mortality was 2.57 (95% confidence interval 1.19 to 5.55).

    CONCLUSION:

    High intakes of calcium in women are associated with higher death rates from all causes and cardiovascular disease but not from stroke.

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  • 43.
    Mohammad, Moman A.
    et al.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Karlsson, Sofia
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Haddad, Jonathan
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Cederberg, Bjorn
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Danderyds Univ Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Frobert, Ole
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Koul, Sasha
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Christmas, national holidays, sport events, and time factors as triggers of acute myocardial infarction: SWEDEHEART observational study 1998-20132018In: The BMJ, E-ISSN 1756-1833, Vol. 363, article id k4811Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES To study circadian rhythm aspects, national holidays, and major sports events as triggers of myocardial infarction.

    DESIGN Retrospective observational study using the nationwide coronary care unit registry, SWEDEHEART.

    SETTING Sweden.

    PARTICIPANTS 283 014 cases of myocardial infarction reported to SWEDEHEART between 1998 and 2013. Symptom onset date was documented for all cases, and time to the nearest minute for 88%.

    INTERVENTIONS Myocardial infarctions with symptom onset on Christmas/New Year, Easter, and Midsummer holiday were identified. Similarly, myocardial infarctions that occurred during a FIFA World Cup, UEFA European Championship, and winter and summer Olympic Games were identified. The two weeks before and after a holiday were set as a control period, and for sports events the control period was set to the same time one year before and after the tournament. Circadian and circaseptan analyses were performed with Sunday and 24:00 as the reference day and hour with which all other days and hours were compared. Incidence rate ratios were calculated using a count regression model.

    MAIN OUTCOME MEASURES Daily count of myocardial infarction.

    RESULTS Christmas and Midsummer holidays were associated with a higher risk of myocardial infarction (incidence rate ratio 1.15, 95% confidence interval 1.12 to 1.19, P<0.001, and 1.12, 1.07 to 1.18, P<0.001, respectively). The highest associated risk was observed for Christmas Eve (1.37, 1.29 to 1.46, P<0.001). No increased risk was observed during Easter holiday or sports events. A circaseptan and circadian variation in the risk of myocardial infarction was observed, with higher risk during early mornings and on Mondays. Results were more pronounced in patients aged over 75 and those with diabetes and a history of coronary artery disease.

    CONCLUSIONS In this nationwide real world study covering 16 years of hospital admissions for myocardial infarction with symptom onset documented to the nearest minute, Christmas, and Midsummer holidays were associated with higher risk of myocardial infarction, particularly in older and sicker patients, suggesting a role of external triggers in vulnerable individuals.

  • 44.
    Mons, Ute
    et al.
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany..
    Mueezzinler, Aysel
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany.;Heidelberg Univ, NAR, Heidelberg, Germany..
    Gellert, Carolin
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany..
    Schoettker, Ben
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany..
    Abnet, Christian C.
    NCI, Bethesda, MD 20892 USA..
    Bobak, Martin
    UCL, Dept Epidemiol & Publ Hlth, London, England..
    de Groot, Lisette
    Wageningen Univ, Div Human Nutr, NL-6700 AP Wageningen, Netherlands..
    Freedman, Neal D.
    NCI, Bethesda, MD 20892 USA..
    Jansen, Eugene
    Natl Inst Publ Hlth & Environm RIVM, Ctr Hlth Protect, Bilthoven, Netherlands..
    Kee, Frank
    Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth, Belfast, Antrim, North Ireland..
    Kromhout, Daan
    Wageningen Univ, Div Human Nutr, NL-6700 AP Wageningen, Netherlands..
    Kuulasmaa, Kari
    Natl Inst Hlth & Welf THL, Helsinki, Finland..
    Laatikainen, Tiina
    Natl Inst Hlth & Welf THL, Helsinki, Finland.;Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.;Hosp Dist North Karelia, Joensuu, Finland..
    O'Doherty, Mark G.
    Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth, Belfast, Antrim, North Ireland..
    Bueno-de-Mesquita, Bas
    Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven, Netherlands.;Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.;Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia..
    Orfanos, Philippos
    Hellen Hlth Fdn, Athens, Greece.;Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece..
    Peters, Annette
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;German Ctr Cardiovasc Dis Res DZHK eV, Munich, Germany..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands..
    Wilsgaard, Tom
    UiT Arctic Univ Norway, Dept Community Med, Tromso, Norway..
    Wolk, Alicja
    Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden..
    Trichopoulou, Antonia
    Hellen Hlth Fdn, Athens, Greece.;Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece..
    Boffetta, Paolo
    Hellen Hlth Fdn, Athens, Greece.;Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA..
    Brenner, Hermann
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany..
    Impact of smoking and smoking cessation on cardiovascular events and mortality among older adults: meta-analysis of individual participant data from prospective cohort studies of the CHANCES consortium2015In: The BMJ, E-ISSN 1756-1833, Vol. 350, article id h1551Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To investigate the impact of smoking and smoking cessation on cardiovascular mortality, acute coronary events, and stroke events in people aged 60 and older, and to calculate and report risk advancement periods for cardiovascular mortality in addition to traditional epidemiological relative risk measures. DESIGN Individual participant meta-analysis using data from 25 cohorts participating in the CHANCES consortium. Data were harmonised, analysed separately employing Cox proportional hazard regression models, and combined by meta-analysis. RESULTS Overall, 503 905 participants aged 60 and older were included in this study, of whom 37 952 died from cardiovascular disease. Random effects meta-analysis of the association of smoking status with cardiovascular mortality yielded a summary hazard ratio of 2.07 (95% CI 1.82 to 2.36) for current smokers and 1.37 (1.25 to 1.49) for former smokers compared with never smokers. Corresponding summary estimates for risk advancement periods were 5.50 years (4.25 to 6.75) for current smokers and 2.16 years (1.38 to 2.39) for former smokers. The excess risk in smokers increased with cigarette consumption in a dose-response manner, and decreased continuously with time since smoking cessation in former smokers. Relative risk estimates for acute coronary events and for stroke events were somewhat lower than for cardiovascular mortality, but patterns were similar. CONCLUSIONS Our study corroborates and expands evidence from previous studies in showing that smoking is a strong independent risk factor of cardiovascular events and mortality even at older age, advancing cardiovascular mortality by more than five years, and demonstrating that smoking cessation in these age groups is still beneficial in reducing the excess risk.

  • 45. Nitsch, Dorothea
    et al.
    Grams, Morgan
    Sang, Yingying
    Black, Corri
    Cirillo, Massimo
    Djurdjev, Ognjenka
    Iseki, Kunitoshi
    Jassal, Simerjot K
    Kimm, Heejin
    Kronenberg, Florian
    Oien, Cecilia M
    Levey, Andrew S
    Levin, Adeera
    Woodward, Mark
    Hemmelgarn, Brenda R
    Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis2013In: The BMJ, E-ISSN 1756-1833, Vol. 346, p. f324-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease.

    DESIGN: Random effects meta-analysis using pooled individual participant data.

    SETTING: 46 cohorts from Europe, North and South America, Asia, and Australasia.

    PARTICIPANTS: 2,051,158 participants (54% women) from general population cohorts (n=1,861,052), high risk cohorts (n=151,494), and chronic kidney disease cohorts (n=38,612). Eligible cohorts (except chronic kidney disease cohorts) had at least 1000 participants, outcomes of either mortality or end stage renal disease of ≥ 50 events, and baseline measurements of estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (mL/min/1.73 m(2)) and urinary albumin-creatinine ratio (mg/g).

    RESULTS: Risks of all-cause mortality and cardiovascular mortality were higher in men at all levels of estimated glomerular filtration rate and albumin-creatinine ratio. While higher risk was associated with lower estimated glomerular filtration rate and higher albumin-creatinine ratio in both sexes, the slope of the risk relationship for all-cause mortality and for cardiovascular mortality were steeper in women than in men. Compared with an estimated glomerular filtration rate of 95, the adjusted hazard ratio for all-cause mortality at estimated glomerular filtration rate 45 was 1.32 (95% CI 1.08 to 1.61) in women and 1.22 (1.00 to 1.48) in men (P(interaction)<0.01). Compared with a urinary albumin-creatinine ratio of 5, the adjusted hazard ratio for all-cause mortality at urinary albumin-creatinine ratio 30 was 1.69 (1.54 to 1.84) in women and 1.43 (1.31 to 1.57) in men (P(interaction)<0.01). Conversely, there was no evidence of a sex difference in associations of estimated glomerular filtration rate and urinary albumin-creatinine ratio with end stage renal disease risk.

    CONCLUSIONS: Both sexes face increased risk of all-cause mortality, cardiovascular mortality, and end stage renal disease with lower estimated glomerular filtration rates and higher albuminuria. These findings were robust across a large global consortium.

  • 46. Nordström, Peter
    et al.
    Gustafson, Yngve
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nordström, Anna
    Length of hospital stay after hip fracture and short term risk of death after discharge: a total cohort study in Sweden2015In: The BMJ, E-ISSN 1756-1833, Vol. 350, article id h696Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate relation between inpatient length of stay after hip fracture and risk of death after hospital discharge.

    SETTING: Population ≥50 years old living in Sweden as of 31 December 2005 with a first hip fracture the years 2006-12.

    PARTICIPANTS: 116 111 patients with an incident hip fracture from a closed nationwide cohort.

    MAIN OUTCOME MEASURE: Death within 30 days of hospital discharge in relation to hospital length of stay after adjustment for multiple covariates.

    RESULTS: Mean inpatient length of stay after a hip fracture decreased from 14.2 days in 2006 to 11.6 days in 2012 (P<0.001). The association between length of stay and risk of death after discharge was non-linear (P<0.001), with a threshold for this non-linear effect of about 10 days. Thus, for patients with length of stay of ≤10 days (n=59 154), each 1-day reduction in length of stay increased the odds of death within 30 days of discharge by 8% in 2006 (odds ratio 1.08 (95% confidence interval 1.04 to 1.12)), which increased to16% in 2012 (odds ratio 1.16 (1.12 to 1.20)). In contrast, for patients with a length of stay of ≥11 days (n=56 957), a 1-day reduction in length of stay was not associated with an increased risk of death after discharge during any of the years of follow up.

    LIMITATIONS: No accurate evaluation of the underlying cause of death could be performed.

    CONCLUSION: Shorter length of stay in hospital after hip fracture is associated with increased risk of death after hospital discharge, but only among patients with length of stay of 10 days or less. This association remained robust over consecutive years.

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  • 47. Pewsner, D
    et al.
    Juni, P
    Egger, M
    Battaglia, M
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bachmann, LM
    Accuracy of electrocardiography in diagnosis of left ventricular hypertrophy in arterial hypertension: systematic review2007In: The BMJ, E-ISSN 1756-1833, Vol. 335, no 7622, p. 711-714CArticle, review/survey (Refereed)
    Abstract [en]

    OBJECTIVE: To review the accuracy of electrocardiography in screening for left ventricular hypertrophy in patients with hypertension. DESIGN: Systematic review of studies of test accuracy of six electrocardiographic indexes: the Sokolow-Lyon index, Cornell voltage index, Cornell product index, Gubner index, and Romhilt-Estes scores with thresholds for a positive test of > or =4 points or > or =5 points. DATA SOURCES: Electronic databases ((Pre-)Medline, Embase), reference lists of relevant studies and previous reviews, and experts. STUDY SELECTION: Two reviewers scrutinised abstracts and examined potentially eligible studies. Studies comparing the electrocardiographic index with echocardiography in hypertensive patients and reporting sufficient data were included. DATA EXTRACTION: Data on study populations, echocardiographic criteria, and methodological quality of studies were extracted. DATA SYNTHESIS: Negative likelihood ratios, which indicate to what extent the posterior odds of left ventricular hypertrophy is reduced by a negative test, were calculated. RESULTS: 21 studies and data on 5608 patients were analysed. The median prevalence of left ventricular hypertrophy was 33% (interquartile range 23-41%) in primary care settings (10 studies) and 65% (37-81%) in secondary care settings (11 studies). The median negative likelihood ratio was similar across electrocardiographic indexes, ranging from 0.85 (range 0.34-1.03) for the Romhilt-Estes score (with threshold > or =4 points) to 0.91 (0.70-1.01) for the Gubner index. Using the Romhilt-Estes score in primary care, a negative electrocardiogram result would reduce the typical pre-test probability from 33% to 31%. In secondary care the typical pre-test probability of 65% would be reduced to 63%. CONCLUSION: Electrocardiographic criteria should not be used to rule out left ventricular hypertrophy in patients with hypertension.

  • 48. Raaschou, Pauline
    et al.
    Simard, Julia F
    Asker Hagelberg, Charlotte
    Askling, Johan
    Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden.2016In: The BMJ, E-ISSN 1756-1833, Vol. 352, article id i262Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the risk of squamous cell and basal cell skin cancer in patients with rheumatoid arthritis naive to biologic drugs, in patients starting tumour necrosis factor (TNF) inhibitor treatment, and in the general population.

    DESIGN: Population based cohort study.

    SETTING: Nationwide data from Sweden.

    PARTICIPANTS: Cohort of patients with rheumatoid arthritis naive to biologics (n=46 409), cohort of patients with rheumatoid arthritis starting TNF inhibitor treatment as first biologic in 1998-2012 (n=12 558), and matched general population comparator cohort, identified through national quality of care and health registers.

    MAIN OUTCOME MEASURE: Hazard ratio of first in situ or invasive squamous cell skin cancer (1998-2012) and first basal cell cancer (2004-12).

    RESULTS: For basal cell cancer, the hazard ratio was 1.22 (95% confidence interval 1.07 to 1.41) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.14 (0.98 to 1.33; 236 v 1587 events) comparing TNF inhibitor treated patients with biologics-naive patients. For squamous cell cancer, the hazard ratio was 1.88 (1.74 to 2.03) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.30 (1.10 to 1.55; 191 v 847 events) comparing TNF inhibitors with biologics-naive patients; the latter translated to an annual number needed to harm in the order of 1600. Among people with a history of squamous cell or basal cell cancer, TNF inhibitors did not further increase risks.

    CONCLUSION: A small to moderately increased risk of basal cell cancer was seen in biologics-naive rheumatoid arthritis patients, with no further effect of TNF inhibitors. For squamous cell cancer, the risk was nearly doubled in biologics-naive patients, with a further 30% increase in risk among patients treated with TNF inhibitors; this translates to one additional case for every 1600 years of treatment experience, assuming that this association reflected causality. Vigilance regarding skin malignancies may be advisable in rheumatoid arthritis, irrespective of TNF inhibitor treatment. Most of the increase in risk for non-melanoma skin cancer in patients with rheumatoid arthritis treated with TNF inhibitors originates from factors other than that treatment.

  • 49. Reizenstein, P
    et al.
    Ljunggren, G
    Smedby, B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Agenäs, I
    Penchansky, M
    Overprescribing iron tablets to elderly people in Sweden1979In: The BMJ, E-ISSN 1756-1833, Vol. 2, no 6196, p. 962-63Article in journal (Refereed)
    Abstract [en]

    Iron should not be prescribed to middle-aged men or older women with anaemia unless the possibility that the iron deficiency is caused by a gastrointestinal tumour has been considered. Thus the prescribing of iron to elderly people was investigated by studying four different prescription statistics and by reviewing records. Over one in 10 women aged over 65 were prescribed iron tablets. Men and women in the oldest age groups were prescribed iron most frequently. The reasons for prescribing iron were examined at a rural health centre. Out of 327 records of patients who were prescribed iron during 1975, 157 were randomly selected and reviewed. Only 18 out of 48 (38%) patients aged 45-75 (men) and 55-75 (women) and 29 out of 109 (27%) aged over 75 years had probable or possible iron-deficiency anaemia as established from the records. Only nine (19%) of the younger patients had a plausible reason for the anaemia other than a bleeding tumour. Ten (9%) of the older patients were considered to be inoperable cases. Thus, according to the records, only 18 (17%) of the patients over 75 years and nine (19%) of those in the younger age group have been prescribed iron. About 70% of all the patients were considered not to have iron deficiency; 7% had had iron deficiency previously, and 20% probably had anaemia as a result of chronic disease; for 43% no real reason for the iron prescription could be found in the record. Thus it is concluded that iron is overprescribed in Sweden, particularly for elderly people. It should not be prescribed until the possibility of a bleeding gastrointestinal tumour has been excluded.

  • 50. Robinson, David
    et al.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Mucci, Lorelei
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stattin, Par
    Use of 5 alpha-reductase inhibitors for lower urinary tract symptoms and risk of prostate cancer in Swedish men: nationwide, population based case-control study2013In: The BMJ, E-ISSN 1756-1833, Vol. 346, p. f3406-Article in journal (Refereed)
    Abstract [en]

    Objective To assess the association between 5 alpha-reductase inhibitor (5-ARI) use in men with lower urinary tract symptoms and prostate cancer risk. Design Nationwide, population based case-control study for men diagnosed with prostate cancer in 2007-09 within the Prostate Cancer data Base Sweden 2.0. Setting The National Prostate Cancer Register, National Patient Register, census, and Prescribed Drug Register in Sweden, from which we obtained data on 5-ARI use before date of prostate cancer diagnosis. Participants 26 735 cases and 133 671 matched controls; five controls per case were randomly selected from matched men in the background population. 7815 men (1499 cases and 6316 controls) had been exposed to 5-ARI. 412 men had been exposed to 5-ARI before the diagnosis of a cancer with Gleason score 8-10. Main outcome measures Risk of prostate cancer calculated as odds ratios and 95% confidence intervals by conditional logistic regression analyses. Results Risk of prostate cancer overall decreased with an increasing duration of exposure; men on 5-ARI treatment for more than three years had an odds ratio of 0.72 (95% confidence interval 0.59 to 0.89; P<0.001 for trend). The same pattern was seen for cancers with Gleason scores 2-6 and score 7 (both P<0.001 for trend). By contrast, the risk of tumours with Gleason scores 8-10 did not decrease with increasing exposure time to 5-ARI (for 0-1 year of exposure, odds ratio 0.96 (95% confidence interval 0.83 to 1.11); for 1-2 years, 1.07 (0.88 to 1.31); for 2-3 years, 0.96 (0.72 to 1.27); for >3 years, 1.23 (0.90 to 1.68); P=0.46 for trend). Conclusions Men treated with 5-ARI for lower urinary tract symptoms had a decreased risk of cancer with Gleason scores 2-7, and showed no evidence of an increased risk of cancer with Gleason scores 8-10 after up to four years' treatment.

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